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Single-cell sequencing reveals αβ chain pairing shapes the T cell repertoire

By Kristina Grigaityte, Jason A Carter, Stephen J Goldfless, Eric W Jeffery, Ronald J Hause, Yue Jiang, David Koppstein, Adrian W Briggs, Kevin M. Esvelt, Francois Vigneault, Gurinder S. Atwal

Posted 02 Nov 2017
bioRxiv DOI: 10.1101/213462

A diverse T cell repertoire is a critical component of the adaptive immune system, providing protection against invading pathogens and neoplastic changes, relying on the recognition of foreign antigens and neoantigen peptides by T cell receptors (TCRs). However, the statistical properties and function of the T cell pool in an individual, under normal physiological conditions, are poorly understood. In this study, we report a comprehensive, quantitative characterization of the T cell repertoire from over 1.9 million cells, yielding over 200,000 high quality paired αβ sequences in 5 healthy human subjects. The dataset was obtained by leveraging recent biotechnology developments in deep RNA sequencing of lymphocytes via single-cell barcoding in emulsion. We report non-random associations and non-monogamous pairing between the α and β chains, lowering the theoretical diversity of the T cell repertoire, and increasing the frequency of public clones shared among individuals. T cell clone size distributions closely followed a power law, with markedly longer tails for CD8+ cytotoxic T cells than CD4+ helper T cells. Furthermore, clonality estimates based on paired chains from single T cells were lower than that from single chain data. Taken together, these results highlight the importance of sequencing αβ pairs to accurately quantify lymphocyte receptor diversity.

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